New method IDs nanomaterials that can cause oxidative damage to cells

Engineered nanomaterials, prized for their
unique semiconducting properties, are already prevalent in everyday consumer
products—from sunscreens, cosmetics, and paints to textiles and solar batteries—and
economic forecasters are predicting the industry will grow into $1 trillion
business in the next few years. But how safe are these materials?

Because the semiconductor properties of
metal-oxide nanomaterials could potentially translate into health hazards for
humans, animals, and the environment, it is imperative, researchers say, to
develop a method for rapidly testing these materials to determine the potential
hazards and take appropriate preventative action.

To that end, University
of California, Los Angeles (UCLA) researchers and their
colleagues have developed a novel screening technology that allows large
batches of these metal-oxide nanomaterials to be assessed quickly, based on
their ability to trigger certain biological responses in cells as a result of
their semiconductor properties. The research is published in ACS Nano.

Just as semiconductors can inject or extract
electrons from industrial materials, semiconducting metal-oxide nanomaterials
can have an electron-transfer effect when they come into contact with human
cells that contain electronically active molecules, the researchers found. And
while these oxidation–reduction reactions are helpful in industry, when they
occur in the body they have the potential to generate oxygen radicals, which
are highly reactive oxygen molecules that damage cells, triggering acute
inflammation in the lungs of exposed humans and animals.

In a key finding, the research team
predicted that metal-oxide nanomaterials and electronically active molecules in
the body must have similar electron energy levels—called band-gap energy in the
case of the nanomaterial—for this hazardous electron transfer to occur and
oxidative damage to result.

Based on this prediction, the researchers
screened 24 metal-oxide nanoparticles to determine which were most likely to
lead to toxicity under real-life exposure. Using a high-throughput screening
assay (performed by robotic equipment and an automated image-capture
microscope), they tested the two dozen materials on a variety of cell types in a
matter of a few hours and found that six of them—those that had previously met
the researchers' predictive criteria for being toxic based on their band-gap
energy—led to oxidative damage in cells.

The team then tested the nanomaterials in
well-orchestrated animal studies and found that only those materials that had
led to oxidative damage in cells were capable of generating inflammation in the
lungs of mice, confirming the researchers' band-gap hypothesis.

"The ability to make such predictions,
starting with cells in a test tube, and extrapolating the results to intact
animals and humans exposed to potentially hazardous metal oxides, is a huge step forward in the safety
screening of nanomaterials," said senior author Dr. Andre Nel, chief of
the division of nanomedicine at the David Geffen School of Medicine at UCLA and
the California NanoSystems Institute at UCLA and director of the University of
California Center for Environmental Implications of Nanotechnology.

According to the researchers, this new
safety-assessment technology has the potential to replace traditional testing,
which is currently performed one material at a time in labor-intensive animal
studies using a "wait-and-see" approach that doesn't reveal why the implicated
nanomaterials could be hazardous. The UCLA team's predictive approach and
screening technique could speed up the ability to assess large numbers of
emerging new nanomaterials rather than waiting for their toxicological
potential to become manifest before action is taken.

"Being able to integrate metal-oxide
electronic properties into a predictive and high-throughput scientific platform
in this work could play an important role in advancing nanomaterial safety
testing in the 21st century to a preventative strategy, rather than waiting for
problems to emerge," Nel said.

Another major advantage of an approach based
on the assessment of nanomaterials' properties is that one can identify those
properties that could potentially be redesigned to make the materials less
hazardous, the researchers said.

The implementation of high-throughput
screening is also leading to the development of computer tools that assist in
prediction-making; in the future, much of the safety assessment of
nanomaterials could be carried out using computer programs that perform smart
modeling and simulation procedures based on electronic properties.

"We can now further refine the testing
of an important class of engineered nanomaterials to the level where regulatory
agencies can make use of our predictions and testing methods," said
Haiyuan Zhang, a postdoctoral research scholar at the Center for Environmental
Implicatioons of Nanotechnology at UCLA's CNSI and the lead author of the
study.